Vinita Kumari, Sripriya Sarangapani, Prathiba Krishnamurthy, Vaitheeswaran Kulothungan, Sathyabaarathi Ravichandran, Rajesh Mahendran, Amali John, Umashankar Vetrivel, Kumaramanickavel Govindasamy, Pal Swakshyar Saumya, Raman Rajiv, Sharma Tarun
SN ONGC Department of Genetics and Molecular Biology, Vision Research Foundation, Chennai, Tamil Nadu, India.
BMJ Open. 2012 Aug 17;2(4). doi: 10.1136/bmjopen-2012-001036. Print 2012.
Elevated levels of intercellular adhesion molecule-1 (ICAM-1) are demonstrated in diabetes complications. The current study aims to understand association of K469E (rs5498) in ICAM-1 gene, in type 2 diabetic (T2D) subjects with retinopathy.
Case-control study.
Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study, an epidemiology study (on prevalence of diabetic retinopathy in T2D subjects (T2DR) from south India) and outpatient department of Sankara Nethralaya, a tertiary care hospital, in Chennai, India.
A total of 356 T2D subjects of >15 years of diabetes duration, with (n=199) and without (n=157) retinopathy.
The rs5498 polymorphism was genotyped by direct sequencing. Multivariate analysis for various clinical covariates was done using SPSS V.14. Comparative assessment of structure stability, folding rate of the variants were assessed using bioinformatics tools like STRIDE, MuPro, ModellerV97, fold rate server, etc.
The AA genotype of rs5498 was seen at a higher frequency in the retinopathy group (p=0.012). The risk for diabetic retinopathy (DR) increased in the presence of AA genotype (OR=1.89-4.82) after the sequential addition of various clinical covariates. Multivariate logistic regression analysis showed 8.26 times high risk for developing DR in the AG genotype (p=0.003). Structural superimposition of ICAM-1 wild type (K469) and variant (E469) showed 0.943 Å of backbone root mean square deviation as calculated by PYMOL software. A difference in the fold rate time was also observed between the wild type (5.4/s) and variant (3.3/s).
This study shows that allele A of rs5498 in ICAM-1 is a putative risk predisposing allele for T2D retinopathy and its clinical covariates in Indian population. The folding rate of the protein decreases for the A allele implicating a potential effect on the structure and function of ICAM-1.
细胞间黏附分子-1（ICAM-1）水平升高在糖尿病并发症中得到证实。本研究旨在了解ICAM-1基因中K469E（rs5498）与2型糖尿病（T2D）视网膜病变患者的关联。
病例对照研究。
桑卡拉奈特拉亚糖尿病视网膜病变流行病学和分子遗传学研究，一项流行病学研究（关于印度南部T2D患者（T2DR）糖尿病视网膜病变的患病率）以及印度钦奈三级护理医院桑卡拉奈特拉亚的门诊部。
总共356名糖尿病病程超过15年的T2D患者，其中有视网膜病变的199例，无视网膜病变的157例。
通过直接测序对rs5498多态性进行基因分型。使用SPSS V.14对各种临床协变量进行多变量分析。使用STRIDE、MuPro、ModellerV97、折叠率服务器等生物信息学工具评估变体的结构稳定性、折叠率的比较评估。
rs5498的AA基因型在视网膜病变组中的出现频率更高（p = 0.012）。在依次添加各种临床协变量后，AA基因型存在时糖尿病视网膜病变（DR）的风险增加（OR = 1.89 - 4.82）。多变量逻辑回归分析显示AG基因型发生DR的风险高8.26倍（p = 0.003）。通过PYMOL软件计算，ICAM-1野生型（K469）和变体（E469）的结构叠加显示主链均方根偏差为0.943 Å。野生型（5.4/s）和变体（3.3/s）之间也观察到折叠率时间的差异。
本研究表明，ICAM-1中rs5498的A等位基因是印度人群中T2D视网膜病变及其临床协变量的一个假定风险易感等位基因。A等位基因使蛋白质的折叠率降低，这意味着对ICAM-1的结构和功能有潜在影响。
